A Pilot Randomized Clinical Trial of Intranasal Oxytocin to Promote Weight Loss in Individuals With Hypothalamic Obesity Journal of the Endocrine Society
Abstract Context Hypothalamic obesity is a rare, treatment-resistant form of obesity. In preliminary studies, the hypothalamic hormone oxytocin (OXT) has shown promise as a potential weight loss therapy. Objective To determine whether 8 weeks of intranasal OXT (vs 8 weeks of placebo) promotes weight loss in children, adolescents, and young adults with hypothalamic obesity. Methods This randomized, double-blind, placebo-controlled, crossover pilot trial ( NCT02849743 ), conducted at an outpatient academic medical center, included patients aged 10 to 35 years with hypothalamic obesity from hypothalamic/pituitary tumors. Participants received intranasal OXT (Syntocinon, 40 USP units/mL, 4 IU/spray) vs excipient-matched placebo, 16 to 24 IU 3 times daily at mealtimes. Weight loss attributable to OXT vs placebo and safety (adverse events) were assessed. Results Of 13 individuals randomized (54% female, 31% pre-pubertal, median age 15.3 years, IQR 13.3-20.6), 10 completed the entire study. We observed a nonsignificant within-subject weight change of −0.6 kg (95% CI: −2.7, 1.5) attributable to OXT vs placebo. A subset (2/18 screened, 5/13 randomized) had prolonged QTc interval on electrocardiography prior to screening and/or in both treatment conditions. Overall, OXT was well-tolerated, and adverse events (epistaxis and nasal irritation, headache, nausea/vomiting, and changes in heart rate, blood pressure, and QTc interval) were similar between OXT and placebo. In exploratory analyses, benefits of OXT for anxiety and impulsivity were observed. Conclusion In this pilot study in hypothalamic obesity, we did not detect a significant impact of intranasal OXT on body weight. OXT was well-tolerated, so future larger studies could examine different dosing, combination therapies, and potential psychosocial benefits. Keywords: oxytocin, neuroendocrinology, hypopituitarism, pediatric endocrinology, hypothalamic obesity, craniopharyngioma
SHOW FULL ABSTRACT CITATION BIBTEX RIS
Shana E McCormack, Zi Wang, Kristin L Wade et al.. A Pilot Randomized Clinical Trial of Intranasal Oxytocin to Promote Weight Loss in Individuals With Hypothalamic Obesity. Journal of the Endocrine Society. (2023). https://doi.org/10.1210/jendso/bvad037 Shana E McCormack, Zi Wang, Kristin L Wade, Anna Dedio, Nicolette Cilenti, Julia Crowley, Franziska Plessow, Vaneeta Bamba, Jeffrey D Roizen, Yaoguang Jiang, Jack Stylli, Arjun Ramakrishnan, Michael L Platt, Karuna Shekdar, Michael J Fisher, Victoria L Vetter, Matthew Hocking, Rui Xiao, Elizabeth A Lawson
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Division of Endocrinology & Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 2
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA 3
Biostatistics & Data Management, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 4
Division of Endocrinology & Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 5
Division of Endocrinology & Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 6
Division of Endocrinology & Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 7
Division of Endocrinology & Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 8
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA 9
Division of Endocrinology & Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 10
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA 11
Division of Endocrinology & Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 12
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA 13
Department of Psychology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA 14
Georgetown University School of Medicine, Washington, DC 20007, USA 15
Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, Uttar Pradesh 208016, India 16
Department of Psychology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA 17
Department of Neuroscience, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA 18
Marketing Department, Wharton School of Business, University of Pennsylvania, Philadelphia, PA 19104, USA 19
Division of Neuroradiology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 20
Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA 21
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA 22
Center for Childhood Cancer Research and Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 23
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA 24
Cardiac Center, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 25
Center for Childhood Cancer Research and Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA 26
Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA 27
Center of Clinical Epidemiology & Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA 28
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA 